Exploring the Long Tail

The migration of datasets online has created a near-infinite inventory for big name retailers such as Amazon and Netflix, giving rise to recommendation systems to assist users in navigating the massive catalog. This has also allowed for the possibility of retailers storing much less popular, uncommon items which would not appear in a more traditional brick-and-mortar setting due to the cost of storage. Nevertheless, previous work has highlighted the profit potential which lies in the so-called long tail\u27\u27 of niche, unpopular items. Unfortunately, due to the limited amount of data in this subset of the inventory, recommendation systems often struggle to make useful suggestions within the long tail, lending them prone to a popularity bias. Our work explores different approaches which recommendation systems typically employ and evaluate the performance of each approach on various subsets of the Netflix Prize data to the end of determining where each approach performs best. We survey collaborative filtering approaches, content-based filtering approaches, and hybrid mechanisms utilizing both of the previous methods. We analyze their behavior on the most popular items, the least popular items, and a composite of the two subsets, and we judge their performance based on the quality of the clusters they produce

Clinical consequences of polypharmacy in elderly.

INTRODUCTION: Polypharmacy, defined as the use of multiple drugs or more than are medically necessary, is a growing concern for older adults. MEDLINE and EMBASE databases were searched from January 1, 1986 to June 30, 2013) to identify relevant articles in people aged \u3e 65 years. AREAS COVERED: We present information about: i) prevalence of polypharmacy and unnecessary medication use; ii) negative consequences of polypharmacy; and iii) interventions to improve polypharmacy. EXPERT OPINION: International research shows that polypharmacy is common in older adults with the highest number of drugs taken by those residing in nursing homes. Nearly 50% of older adults take one or more medications that are not medically necessary. Research has clearly established a strong relationship between polypharmacy and negative clinical consequences. Moreover, well-designed interprofessional (often including clinical pharmacist) intervention studies that focus on enrolling high-risk older patients with polypharmacy have shown that they can be effective in reducing aspects of unnecessary prescribing with mixed results on distal health outcomes

Approche réactive pour la conduite en convoi des véhicules autonomes (Modélisation et vérification)

Cette thèse se situe dans la problématique de la conduite en convoi de véhicules autonomes : des ensembles de véhicules qui se déplacent en conservant une configuration spatiale, sans aucune accroche matérielle. Ses objectifs sont d'abord, la définition d'une approche de prise de décision pour les systèmes de convois de véhicules, puis, la définition d'une approche de vérification, adaptée à la preuve de propriétés relatives aux convois de véhicules, avec une attention particulière envers les propriétés de sûreté.L'approche pour la prise de décision est décentralisée et auto organisée : chaque véhicule détermine son comportement de façon locale, à partir de ses propres capacités de perception, sans avoir recours à une communication explicite, de telle sorte que l'organisation du convoi, son maintien et son évolution soient le résultat émergeant du comportement de chaque véhicule. L'approche proposée s'applique a des convois suivant plusieurs types de configuration, et permet des changements dynamiques de configuration.L'approche proposée pour la vérification de propriétés de sûreté des convois de véhicules, adopte le model-checking comme technique de preuve. Pour contourner le problème de l'explosion combinatoire, rencontré dans la vérification des systèmes complexes, nous avons proposé une méthode compositionnelle de vérification, qui consiste a décomposer le système en sous systèmes et à associer une propriété auxiliaire à chacun des sous systèmes. La propriété globale sera ensuite déduite de l'ensemble des propriétés auxiliaires, par l'application d'une règle de déduction compositionnelle. La complexité calculatoire est mieux maîtrisée car le model-checking s'applique aux sous-systèmes. Nous proposons une règle de déduction adaptée aux systèmes de conduite en convoi, en particulier ceux qui sont basés sur des approches décentralisées. La règle considère chaque véhicule comme un composant. Elle est consistante sous la condition que l'ajout d'un nouveau composant au système n'a pas d'influence sur le comportement du reste du système. L'approche décentralisée proposée pour la conduite en convoi satisfait cette condition. Deux propriétés de sûreté ont été vérifiées : absence de collision et évolution confortable pour les passagersThis thesis places in the framework of Platoons, sets of autonomous vehicles that move together while keeping a spatial configuration, without any material coupling. Goals of the thesis are: first, the definition of a decision making approach for platoon systems. Second, the definition of a method for the verification of safety properties associated to the platoon system.The proposed decision making approach is decentralized and self-organized. Platoon vehicles are autonomous, they act based only on their perception capabilities. The configuration emerges as a result of the individual behavior of each of the platoon vehicle. The proposed approach can be applied to platoon with different configurations, and allows for dynamic change of configuration.The proposed verification method uses the model-checking technique. Model checking of complex system can lead to the combinatory explosion problem. To deal with this problem, we choose to use a compositional verification method. Compositional methods decompose system models into different components and associate to each component an auxiliary property. The global property can then be deduced from the set of all the auxiliary properties, by applying a compositional deduction rule. We define a deduction rule suitable for decentralised platoon systems. The deduction rule considers each vehicle as a component. It is applicable under the assumption that adding a new component to an instance of the system does not modify behavior of the instance. Two safety properties have been verified : collision avoidance.BELFORT-UTBM-SEVENANS (900942101) / SudocSudocFranceF

Bone Morphogenetic Protein‐2 Decreases MicroRNA‐30b and MicroRNA‐30c to Promote Vascular Smooth Muscle Cell Calcification

Background: Vascular calcification resembles bone formation and involves vascular smooth muscle cell (SMC) transition to an osteoblast‐like phenotype to express Runx2, a master osteoblast transcription factor. One possible mechanism by which Runx2 protein expression is induced is downregulation of inhibitory microRNAs (miR). Methods and Results: Human coronary artery SMCs (CASMCs) treated with bone morphogenetic protein‐2 (BMP‐2; 100 ng/mL) demonstrated a 1.7‐fold (P<0.02) increase in Runx2 protein expression at 24 hours. A miR microarray and target prediction database analysis independently identified miR‐30b and miR‐30c (miR‐30b‐c) as miRs that regulate Runx2 expression. Real‐time–polymerase chain reaction confirmed that BMP‐2 decreased miR‐30b and miR‐30c expression. A luciferase reporter assay verified that both miR‐30b and miR‐30c bind to the 3′‐untranslated region of Runx2 mRNA to regulate its expression. CASMCs transfected with antagomirs to downregulate miR‐30b‐c demonstrated significantly increased Runx2, intracellular calcium deposition, and mineralization. Conversely, forced expression of miR‐30b‐c by transfection with pre–miR‐30b‐c prevented the increase in Runx2 expression and mineralization of SMCs. Calcified human coronary arteries demonstrated higher levels of BMP‐2 and lower levels of miR‐30b than did noncalcified donor coronary arteries. Conclusions: BMP‐2 downregulates miR‐30b and miR‐30c to increase Runx2 expression in CASMCs and promote mineralization. Strategies that modulate expression of miR‐30b and miR‐30c may influence vascular calcification

Guidelines for translational research in heart failure

Heart failure (HF) remains a major cause of death and hospitalization worldwide. Despite medical advances, the prognosis of HF remains poor and new therapeutic approaches are urgently needed. The development of new therapies for HF is hindered by inappropriate or incomplete preclinical studies. In these guidelines, we present a number of recommendations to enhance similarity between HF animal models and the human condition in order to reduce the chances of failure in subsequent clinical trials. We propose different approaches to address safety as well as efficacy of new therapeutic products. We also propose that good practice rules are followed from the outset so that the chances of eventual approval by regulatory agencies increase. We hope that these guidelines will help improve the translation of results from animal models to humans and thereby contribute to more successful clinical trials and development of new therapies for HF.European Union [CardioNeT-ITN-289600, CardioNext-ITN-608027, FP7-IMI-JU-SAFET-115003]; Spanish Ministry of Economy [SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Spanish Ministry of Economy; Pro-CNIC Foundation; NIH [HL-120732, HL100401]; AHA [14SFRN20740000]; CPRIT [RP110486P3]; Leducq Foundation [11CVD04]; MINECO-SAF [2013-42962R]; Instituto Carlos III [TERCEL-RD-12/00190026, RIC12/00420024]S

Distinct Roles of MicroRNA-1 and -499 in Ventricular Specification and Functional Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes

BACKGROUND: MicroRNAs (miRs) negatively regulate transcription and are important determinants of normal heart development and heart failure pathogenesis. Despite the significant knowledge gained in mouse studies, their functional roles in human (h) heart remain elusive. METHODS AND RESULTS: We hypothesized that miRs that figure prominently in cardiac differentiation are differentially expressed in differentiating, developing, and terminally mature human cardiomyocytes (CMs). As a first step, we mapped the miR profiles of human (h) embryonic stem cells (ESCs), hESC-derived (hE), fetal (hF) and adult (hA) ventricular (V) CMs. 63 miRs were differentially expressed between hESCs and hE-VCMs. Of these, 29, including the miR-302 and -371/372/373 clusters, were associated with pluripotency and uniquely expressed in hESCs. Of the remaining miRs differentially expressed in hE-VCMs, 23 continued to express highly in hF- and hA-VCMs, with miR-1, -133, and -499 displaying the largest fold differences; others such as miR-let-7a, -let-7b, -26b, -125a and -143 were non-cardiac specific. Functionally, LV-miR-499 transduction of hESC-derived cardiovascular progenitors significantly increased the yield of hE-VCMs (to 72% from 48% of control; p0.05). By contrast, LV-miR-1 transduction did not bias the yield (p>0.05) but decreased APD and hyperpolarized RMP/MDP in hE-VCMs due to increased I(to), I(Ks) and I(Kr), and decreased I(f) (p<0.05) as signs of functional maturation. Also, LV-miR-1 but not -499 augmented the immature Ca(2+) transient amplitude and kinetics. Molecular pathway analyses were performed for further insights. CONCLUSION: We conclude that miR-1 and -499 play differential roles in cardiac differentiation of hESCs in a context-dependent fashion. While miR-499 promotes ventricular specification of hESCs, miR-1 serves to facilitate electrophysiological maturation.published_or_final_versio

Fracture Risk in Men With Congestive Heart Failure Risk Reduction With Spironolactone

ObjectivesThe purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF).BackgroundIn rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known.MethodsThe medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of having a fracture associated with spironolactone use were estimated using conditional logistic regression.ResultsWe identified 167 cases with a single-incident fracture and matched these by age and race to 668 control subjects without fractures. After adjustment for covariates, spironolactone use was inversely associated with total fracture (odds ratio: 0.575; 95% confidence interval: 0.346 to 0.955, p = 0.0324).ConclusionsThe use of spironolactone is inversely associated with fractures in men with CHF